Forfeited hepatogenesis program and increased embryonic stem cell traits in young hepatocellular carcinoma (HCC) comparing to elderly HCC

Hsei Wei Wang, Tsung Han Hsieh, Ssu Yi Huang, Gar Yang Chau, Chien Yi Tung, Chien Wei Su, Jaw Ching Wu

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

Background: Hepatocellular carcinoma (HCC) in young subjects is rare but more devastating. We hypothesize that genes and etiological pathways are unique to young HCC (yHCC; ≤40 years old at diagnosis) patients. We therefore compared the gene expression profiles between yHCCs and HCCs from elderly patients.Results: All 44 young HCCs (≤40 years old at the diagnosis; 23 cases in the training set while another 21 in the validation cohort) were positive for serum hepatitis B surface antigen (HBsAg), but negative for antibodies to hepatitis C virus (anti-HCV). All 48 elderly (>40 years old; 38 in the training set while another 10 in the validation cohort) HCC patients enrolled were also serum HBsAg positive and anti-HCV negative. Comparative genomics analysis was further performed for elucidating enriched or suppressed biological activities in different HCC subtypes. The yHCC group showed more macroscopic venous invasions (60.9% vs. 10.5%, p < 0.001), fewer associated cirrhosis (17.4% vs. 63.2%, p < 0.001), and distinct profiles of expressed genes, especially those related to DNA replication and repair. yHCCs possessed increased embryonic stem cell (ESC) traits and were more dedifferentiated. A 309-gene signature was obtained from two training cohorts and validated in another independent data set. The ILF3 ESC gene, which was previously reported in poorly differentiated breast cancers and bladder carcinomas, was also present in yHCCs. Genes associated with HCC suppression, including AR and ADRA1A, were less abundant in yHCCs. ESC genes were also more enriched in advanced HCCs from elderly patients.Conclusion: This study revealed the molecular makeup of yHCC and the link between ESC traits and HCC subtypes. Findings in elderly tumors, therefore, cannot be simply extrapolated to young patients, and yHCC should be treated differently.

Original languageEnglish
Article number736
JournalBMC Genomics
Volume14
Issue number1
DOIs
Publication statusPublished - Oct 26 2013
Externally publishedYes

Keywords

  • Dedifferentiation
  • Embryonic stem cells
  • Young hepatocellular carcinoma

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

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